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How do bacteria perceive their environment? How do they find and detect nutrients? How do they eat? These are some of the questions first broached by the work of François Jacob and Jacques Monod with their seminal studies showing how bacteria detect lactose in their environment and regulate their gene expression accordingly. It was this work which led to the discovery of the lac operon: the basic unit of DNA necessary for the transport and metabolism of lactose, which is under the control of a molecular regulator. This was the discovery that earned the two researchers the Nobel Prize for Medicine in 1965. This regulator was first proposed to be RNA but the lactose operon regulator was ultimately shown to be a protein, the famous Lac repressor. However, it turns out this is not always the case.
In an article published in the journal Science, researchers from the Bacteria-Cell Interactions Unit, led by Pascale Cossart (Institut Pasteur, INSERM, INRA), reveal a new system of gene regulation in Listeria monocytogenes, the bacteria in food and responsible for listeriosis. Researchers have discovered how Listeria monocytogenes is able to detect the presence of a molecule called "ethanolamine" that bacteria can use as a nutrient source in the human host, and regulate gene expression accordingly. Ethanolamine is derived from the degradation of phosphatidylethanolamine in mammalian cell membranes and is known to serve as a nutrient for certain pathogens such as Salmonella in the intestine.
It was known that Listeria like Salmonella requires a cofactor, Vitamin B12, to use and degrade ethanolamine. Researchers now show that to account for this, the bacterium has developed a unique mechanism that allows it to wait until vitamin B12 and ethanolamine are present at the same time, before activating expression of the ethanolamine utilization operon. The beauty of the system is that this control is orchestrated by a non-coding RNA which may be present in two forms - a short or a long - depending on whether the vitamin B12 is present or not. Vitamin B12 binds directly to the end of the RNA via an element termed a “riboswitch”. In the absence of B12, the riboswitch causes the RNA to be produced in a long form that can bind and sequester the activator genes the use of ethanolamine whereas in the presence of B12, the riboswitch causes the RNA to be produced in a short which can no longer sequester the activator and thus frees it to activate the ethanolamine utilization genes.
These results describe a new mechanism of gene regulation that influences the pathogenicity of the important human pathogen Listeria monocytogenes.
Illustration: Listeria invading an epithelial cell. © Institut Pasteur
Sequestration of a two-component response regulator by a riboswitch regulated non-coding RNA, Science, August 22, 2014, DOI : 10.1126/science.1255083
J.R. Mellin1 2 3, Mikael Koutero1 2 3, Daniel Dar 4, Marie-Anne Nahori1 2 3, Rotem Sorek4, Pascale Cossart1 2 3
1 Institut Pasteur, Unité des Interactions Bactéries-Cellules, Paris, F-75015 France.
2 INSERM, U604, Paris, F-75015 France.
3 INRA, USC2020, Paris, F-75015 France.
4 Weizmann Institute of Science, Department of Molecular Genetics, Rehovot, Israel